# Malaria parasite determinants of host cell tropism

> **NIH NIH R01** · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · 2022 · $837,848

## Abstract

PROJECT SUMMARY
Malaria continues to be a major scourge of humanity, and is caused by infection of red blood cells (RBCs) by
the protozoan Plasmodium spp. parasites. Plasmodium falciparum can achieve high parasite biomasses in the
circulation causing severe morbidity and mortality. Blood-stage parasites have a strict cellular tropism for RBCs,
interacting with numerous molecular determinants in the RBCs for productive infection and transmission.
Parasite polymorphisms that allow parasites to propagate and persist in different types of RBCs present a major
challenge to malaria control and elimination. This includes the ability of the invasive merozoite forms to use
different receptors on RBCs, known as invasion pathways. We will leverage the power of forward genetics to
identify the molecular determinants mediating two key features of the cellular tropism of P. falciparum: RBC age
and RBC species preference. We have found that different P. falciparum strains vary significantly in these
preferences, and hypothesize that the parasite polymorphisms underlying this variation are critical to the
emergence and persistence of P. falciparum in human populations, and are key determinants of pathogenesis
and transmission. We will employ a forward genetics approach to identify polymorphisms and genes associated
with RBC age and species preference, specifically Bulk Segregant Analysis (BSA) of progeny from genetic
crosses of P. falciparum parental lines with varying invasion preferences. Reverse genetics approaches will be
used for the functional analysis of naturally occurring polymorphisms in candidate genes, both singly and in
combination. Together these studies will provide a comprehensive understanding of the molecular basis of
cellular tropism in P. falciparum parasites, focused on RBC age and species preference. In the long-term we
hope that our studies will elucidate the critical interactions required for the persistence, pathogenicity and
transmission of P. falciparum in parasite populations, to inform public health interventions and inform vaccine
development.

## Key facts

- **NIH application ID:** 10522253
- **Project number:** 1R01AI165755-01A1
- **Recipient organization:** HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH
- **Principal Investigator:** Manoj T Duraisingh
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $837,848
- **Award type:** 1
- **Project period:** 2022-07-01 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10522253

## Citation

> US National Institutes of Health, RePORTER application 10522253, Malaria parasite determinants of host cell tropism (1R01AI165755-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10522253. Licensed CC0.

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